Abstract
The utilization of nanomaterials in the biosensor field has garnered substantial attention in recent years. Initially, the emphasis was on enhancing the sensor current rather than material interactions. However, carbon nanotubes (CNTs) have gained prominence in glucose sensors due to their high aspect ratio, remarkable chemical stability, and notable optical and electronic attributes. The diverse nanostructures and metal surface designs of CNTs, coupled with their exceptional physical and chemical properties, have led to diverse applications in electrochemical glucose sensor research. Substantial progress has been achieved, particularly in constructing flexible interfaces based on CNTs. This review focuses on CNT-based sensor design, manufacturing advancements, material synergy effects, and minimally invasive/noninvasive glucose monitoring devices. The review also discusses the trend toward simultaneous detection of multiple markers in glucose sensors and the pivotal role played by CNTs in this trend. Furthermore, the latest applications of CNTs in electrochemical glucose sensors are explored, accompanied by an overview of the current status, challenges, and future prospects of CNT-based sensors and their potential applications.
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Introduction
Hyperglycemia due to insulin shortage or insulin resistance is characteristic of diabetes, and is often known as diabetes mellitus [1]. Approximately 537 million individuals worldwide currently have diabetes. The number of individuals with diabetes is rising and is predicted to exceed 783 million by 2045 [2]. Glucose monitoring is a crucial component of clinical diagnostics for diabetes management [3]. Due to the high number of diabetic patients infected with COVID-19, the current coronavirus pandemic has also heightened interest in glucose control and monitoring [4]. Blood is the most common and traditional biofluid for glucose detection. However, blood collection is invasive and, therefore, uncomfortable and inconvenient for users. In recent years, advances in nanotechnology, microfluidics, and point-of-care (POC) sensing technologies, have prompted researchers to investigate alternative biofluids, such as sweat, urine, saliva, and interstitial fluid (ISF), for noninvasive, continuous, and wearable glucose monitoring [5].
Given its low cost, quick response, and user-friendliness, electrochemical analysis has attracted considerable interest in the application of glucose sensors [39].
Various methods exist for producing CNTs, with arc discharge, chemical vapor deposition, and laser ablation being the most common (Fig. 2B–D). Each method has its advantages and disadvantages, as detailed in Table 1. Different synthesis methods will synthesize CNTs of different lengths and diameters. Studies have shown that CNTs with larger length-to-diameter ratios will have higher electrical conductivity [40, 41]. From Table 1, it can be inferred that CVD can synthesize CNTs with larger length-to-diameter ratio and higher electrical conductivity. As the performance of CNT-based glucose sensors is closely related to conductivity and CVD method has the potential to synthesize CNTs on a large scale, CVD may be the most promising of the current CNT synthesis methods. The future use of single-walled CNTs (SWCNTs) in electronic devices relies on obtaining pure, semiconducting SWCNTs. Commercial CNT feedstocks contain CNTs of different diameters and chirality. Techniques such as dielectric electrophoresis, density gradient ultracentrifugation, and surfactant or polar biopolymer dispersion have been developed for SWCNT separation. Conjugated polymer wrap** is a promising purification and identification strategy [42]. The strategy, with the polymer’s π-conjugated backbone interacting with the π–electron filled 2D surface of the nanotubes, thereby facilitating the break-up and dispersion of the optimal length of soluble alkyl side chains in organic solvents. The intricate structural design of the conjugated polymers allows for the selective assignment of SWCNTs with sizeable diameters or specific chirality [76]. However, this system requires an oxidized mediator for oxidase regeneration [77]. To address this limitation, Juska et al. [78] presented a biosensor based on a gold ribbon array electrode with GOx and HRP. The electrodeposited gold foam increased the active surface area, enabling stable glucose detection for approximately 45 days (Fig. 4A). This sensing platform demonstrated long-term stability for glucose detection for approximately 45 days.
A Description of a 2-step electrochemical deposition process for the fabrication of Au-foam/CS-MWCNT electrodes. Reprinted with permission from Ref. [78]. B Illustration of SMEN’s thermal stability (65 °C) and resistance to organic solvents. Reprinted with permission from Ref. [79]. C Schematic illustration of GOx@ PAVE-MWCNTs NCs glucose biosensor fabrication. Reprinted with permission from Ref. [80]. D Glucose detection mechanism of GOx/AuNP/PANI/rGO/NH2-MWCNTs biosensor. Reprinted with permission from Ref. [84]. E Schematic representation of the PPG@Ru@UiO-66-NH2 sensor fabrication process and the glucose electrocatalytic reaction at the electrode interface. Reprinted with permission from Ref. [91]
To ensure enzyme performance under harsh conditions, Dhanjai et al. [79] employed highly stable single-molecule enzyme nanocapsules (SMEN), rather than natural enzymes, as biometric components (Fig. 4B). The stability of the proposed SMEN-based biosensors was assessed under a range of operating conditions. Following 4 h of incubation at an elevated temperature (65 °C), the biosensor employing natural GOx lost its glucose oxidation catalytic activity. In contrast, the nGOx/N-CNT-Chi/GCE biosensor retained 56% of its initial activity. This method represents a novel and promising direction in the pursuit of robust biosensors for a multitude of applications.
Inspired by efficient molecular imprinting strategies for small molecules, Xu et al. [80] modified MWCNTs with polymeric NPs laden with enzymes to create a highly sensitive enzymatic sensing platform (Fig. 4C). The amphiphilic copolymer poly [acrylic acid-r-(7-(4-vinylbenzyloxy)-4-methyl coumarin)-r-ethylhexyl acrylate] (PAVE), which contained photocrosslinkable coumarin chain segments and carboxyl groups, was co-assembled with MWCNTs in an aqueous solution while encapsulating Gox to produce necklace-like bio-nanocomposites (GOx@PAVE-CNTs). The polymeric NPs laden with GOx were nanobeads, whereas the MWCNTs were conductive threads. The GOx@PAVE-CNT bio-nanocomposite was subsequently electrodeposited onto the electrode surface and, following photocrosslinking, formed a porous network-structured biosensing composite film. The biosensor exhibited a low LOD (0.36 μM) and ultrafast response (< 3 s) for glucose detection.
Metallic nanomaterials possess stable electrochemical properties and high catalytic activity, making them ideal candidates for maintaining biological component activity while facilitating electron transfer between proteins and electrodes. When combined with CNTs, metallic nanomaterials can exhibit improved interference resistance, sensitivity, selectivity, and stability given their compatibility with proteins [81, 82]. Zeng et al. [83] synthesized an amperometric glucose sensor through layer-by-layer assembly of MWCNTs, PANI, and AuNPs on a PTFE/GOx/AuNP/PANI/MWCNT/GCE substrate to construct a fixed GOx carrier. The synergistic effect of AuNPs, PANI, and MWCNTs reduced the molecular diffusion distance and improved the charge transfer efficiency, enabling direct electron transfer for the immobilized enzyme. Debasis et al. [84] immobilized GOx on MWCNT/PANI/graphene oxide (GO)/AuNP-functionalized SPCE to develop a highly sensitive glucose biosensor with a reduction current 13.43 times higher than that of naked SPCE and lower working potential. The glucose reaction with GOx (FAD) produced gluconolactone and GOx (FADH2), followed by the reaction of GOx (FADH2) with dissolved oxygen to form H2O2 and GOx (FAD) (Fig. 4D). The decomposition of H2O2 amplified the response, and the biosensor was validated for detecting glucose levels in human blood serum samples. To avoid oxygen use, Navaee et al. [85] designed a new platform by grafting thiamine acid and Au NPs onto amino CNT/graphene carriers in a 3D framework, followed by ultrasonic processing to arrange methionine and Au NPs as nanorods in a MOF. Electrochemical processing effectively intercepted the enzyme and facilitated subsequent electron transfer, resulting in a highly sensitive bioelectrode.
MOFs are a new category of hybrid porous materials consisting of metal ions and organic linkers with unique features including high specific surface area, size adjustable pore size, multi-functionality and high drug loading efficiency [86, 87]. MOF-based nanozymes have been extensively utilized for enzyme immobilization by using various techniques, such as absorption, covalent linkage, pore encapsulation, and coprecipitation, to preserve the enzymes’ accessibility, activity, and physical constraints [88]. To address the low conductivity of MOFs, CNTs have been introduced to enhance the electronic transmission efficiency. For instance, Song et al. [89] developed Tb@mesoMOFs on the surface of CNTs to create a Tb@mesoMOF-CNT nanocomposite, which served as a support substrate for electrochemical glucose biosensors. The use of a novel electron mediator, methylene green, and an electrocatalyst, GDH, loaded onto the surface of a GCE resulted in excellent glucose detection performance with a linear range of 25 μM to 17 mM and a LOD of 8 μM. Moreover, Dang et al. [90] prepared a mixture of metal–organic skeleton (Fe, Mn) and Au NP-anchored CNT (Au/MOFs(Fe, Mn)/CNT) by using a one-step hydrothermal method. Incorporating CNTs into graphene paper improved the conductivity, mechanical strength, and surface roughness of the flexible nanohybrid electrodes. The increased active sites of AuNPs/MOF/CNTs resulted in a enhanced peroxidase-like activity, allowing an rise on partial charge density and electron transport between the Fermi levels of MOF, Au NPs, and CNTs. Based on the cascade reaction of artificial peroxidase and GOx, glucose can be detected with increased sensitivity and specificity in the linear range of 0.005–0.3 μM with a LOD of 0.002 μM. In addition, a novel glucose sensor immobilizing GOx on a conjugated polymer and MOF composite based on ruthenium was reported [91]. A prefabricated water-soluble conjugated polymer (poly(n-phenylglycine)) and a MOF (UiO-66-NH2) were used to create PPG@Ru@UiO-66-NH2 via controlled chemistry synthesis (Fig. 4E). The carbonyl and amide groups on the conjugated polymer and MOF surfaces cross-linked GOx, reducing Surface carbonyl and amide groups on conjugated polymers and metal–organic frameworks (MOFs) cross-linked GOx, reducing the immobilisation potential to 0.2 V and boosting the active surface area. The PPG@Ru@UiO-66-NH2/GOx-coated electrode displayed a LOD of 5 μM. These MOF-based biosensors demonstrated a potential for further applications in biosensing and bioelectronics, including medical diagnostics, environmental monitoring, and food safety. A brief overview of other reported important CNT-based enzymatic glucose sensors is summarized in Table 2.
Recent developments in CNT-based nonenzymatic glucose sensors
To address the limitations of enzymatic sensors, such as susceptibility to temperature, pH, humidity and chemical instability, nonenzymatic sensors have emerged as a promising alternative for glucose sensing [161]. These systems often target body fluids such as saliva, sweat, ISF, and urine. CNTs, with their high electroconductivity, offer promising possibilities for integration with various metals and polymers, enhancing noninvasive glucose monitoring. CNTs play a crucial role in improving flexibility and conductivity in wearable applications. For instance, MWCNTs can form bridges with silver nanowires in a hybrid network, preventing fracture under bending strain [162]. Highly stretchable conductive CNTs and polyurethane nanofiber spiral yarns have also been developed, demonstrating stable conductivity and recovery during deformation [163]. The firm winding of CNTs was utilized to form a more stable conductive network, resulting in a yarn with stable conductivity and recovery in the 900% deformation range, and maintaining conductivity when stretched to 1700%. Buckypaper, a CNT-based paper-like membrane, has shown potential for flexible and wearable electrochemical devices, contributing to innovative medical device and wearable technology development [164]. This holds significant implications for the development of innovative technologies in the field of medical devices and wearables.
Human sweat, containing valuable biomarkers, holds promise for noninvasive health status monitoring [165]. Glucose can diffuse from blood into sweat, establishing a connection between blood glucose and sweat glucose levels [166]. Compared to other body fluids, such as blood, ISF, and urine, sweat glucose can be more conveniently detected by biosensors [167, 168]. **a et al. [169] introduced a mediator-free wearable biosensor for real-time glucose sensing in sweat (Fig. 6D). They developed a flexible and hierarchical meso/macroporous film comprising CNTs and ethylene–vinyl acetate (EVA) copolymer as the sensing substrate. The film's 3D conductive nanoporous structure enabled direct electron transfer-based electrocatalysis, eliminating the need for a mediator in glucose monitoring. The CNT-EVA film was functionalized with a GOx-HRP bienzyme, resulting in biosensors with exceptional selectivity and high sensitivity (270 ± 10 μA mM−1 cm−2).
Based on the stretchable nonenzymatic AuNS/CNT electrode, Oh et al. [170] created a wearable electrochemical biosensor based on a stretchable nonenzymatic AuNS/CNT electrode to detect glucose and pH in sweat. CoWO4 NPs were immobilized on CNTs with a large surface area, enabling selective glucose detection without interference from other chemical components and ions in sweat. This biosensor exhibited long-term stability over 10 days without a significant decrease in sensitivity.
With the study of MXene nanomaterials emerging as a focal point of interest, MXenes exhibit unparalleled potential for application in glucose biosensors. Glucose biosensors displaying high sensitivity, extensive detection range, excellent thermal stability, and dependable selectivity are now in development [171]. As a representative member of the MXene family, Ti3C2Tx MXene, known for its metallic conductivity, manifests remarkable electrochemical activity and supports the immobilization of biomolecules, advantages that are conducive to creating sensors for various diagnostic applications [172]. Leveraging Ti3C2Tx MXene nanocomposites, Lei et al. [173] engineered a stretchable, wearable, and modular multifunctional biosensor. This device, incorporating a novel Ti3C2Tx/Prussian blue (Ti3C2Tx/PB) composite, was designed for the simultaneous monitoring of sweat glucose, lactate, and pH. Recognizing that the limited oxygen supply in the enzymatic reaction zone could restrict the upper detection limit, linearity, sensitivity, and accuracy according to Fick’s law, the team designed biosensors with open-air pores. These pores form a solid–liquid–air three-phase interface, allowing a consistent oxygen supply and achieving a higher sensitivity of 35.3 μA mM−1 cm−2 for glucose detection. Furthermore, the simultaneous monitoring of pH values enhances the accuracy of the sensors by adjusting glucose and lactate concentrations through the calibration plot for different pH values. During electrode fabrication, the Ti3C2Tx/PB hybrid nanosheets intermingled with each other, and CNTs became entangled, resulting in nested structures within the restacked Ti3C2Tx/PB layers. Interestingly, the combination of CNTs and CaCO3 particles, followed by dissolution in hydrochloric acid, produced a porous and ultrathin film, enhancing oxygen transport. The ensuing intercalation and winding of CNTs through the layers yielded larger surface-active sites, aiding enzyme immobilization. Impressively, the glucose sensor demonstrated consistent stability, with negligible current fluctuation over 15 days without additional calibrations.
Nadtinan Promphet et al. [174] reported on a wristwatch sensor designed for the real-time, simultaneous detection of glucose and lactate in sweat. The cotton thread electrode was modified with cellulose nanofibers, CNT ink, PB, and chitosan to enhance liquid adsorption, bioreceptor immobilization, and sensor performance while concurrently minimizing skin irritation. In this study, the use of water-based CNT ink facilitated a more straightforward coating process due to its low viscosity, which led to more profound penetration into the cotton thread-based working electrode. PB was added to the CNT ink to further enhance the electrocatalytic properties of the thread-based electrode. The wristwatch sensing device offers a linear range of 0.025–3 × 10–3 m with a detection limit of 0.025 × 10−3 m for glucose, a phenomenon that can likely be ascribed to the remarkable synergy between GOx and CNT ink-PB-modified conductive thread-based electrodes. Notably, the current responses for glucose and lactate remained above 80% after 28 days, possibly due to the chitosan membrane on the thread-based electrode, which aids in preserving the enzymatic activity of both enzymes.
ISF-based noninvasive blood glucose sensors typically require the construction of at least three or more electrodes, complicating the device design [175, 176]. To streamline the fabrication process, Yao et al. [177] devised a wearable noninvasive glucose sensor utilizing a G/CNT/GOx composite textile for the working electrode and a G/CNT/Ag/AgCl composite textile for the counter electrode (Fig. 6E). The CNTs acted as efficient conducting platforms for GOx, marking the first integration of ISF extraction and blood glucose monitoring modules into a unified device, resulting in semicontinuous blood glucose observation. The textile-like electrodes confer these sensors with great flexibility and wearability, thereby permitting integration with other electronic components for comprehensive human health management and monitoring.
The advancement of saliva testing heralds an era of noninvasive and pain-free glucose assessment. Lin et al. [178] engineered a novel electrode for saliva-based, noninvasive glucose sensing. CNTs were cultivated via chemical vapor deposition on a glass substrate coated with FTO, followed by GO immobilization using electrostatic force and polyethylenimine (PEI). This study revealed that the CNT forest substantially bolstered charge transfer, and the networked CNT forest structure facilitated stable immobilization of substantial quantities of GOx on the rough electrode surface. The FTO-CNT/PEI/GOx electrode exhibited a sensitivity of 63.38 μA mM−1 cm−2 with a wide linear range of 70–700 µM glucose. Moreover, a synergetic effect generated by SWCNTs, GO (rGO), and cobalt phthalocyanine (CoPc) facilitated the creation of a SWCNT/rGO/CoPc GCE for the nonenzymatic detection of glucose in saliva, presenting a sensitivity of 992.4 μA mM−1 cm−2 and specificity for glucose in a complex interference environment [179] (Fig. 6F).
In the arena of diaper-based sensors, which have attracted considerable attention, there is still scant exploration of biomolecular strategies for in situ urine sensing, a deficiency that hampers the collection of health-evaluation information from the user’s urine. Li et al. [180] introduced a smart diaper that employs integrated multiplex electrochemical sensors (MECSs) for in situ urine analysis, selectively monitoring glucose levels. The electrode arrays embedded in the mechanically flexible diaper were tailored with CNT coatings and other chemicals, such as ion-selective membranes, enzymes, and Pt NPs, to scrutinize the target biomarkers correlated with urine (Fig. 6G). Furthermore, MECSs may be fashioned into prototypes, comprising a flexible circuit board and a Bluetooth signal transmitter, serving as an alternative means of bedside monitoring for patients, infants, and elderly individuals. Wang et al. [181] developed an innovative multi-calibrated glucose potentiometric (MCGP) sensing array, fusing a glucose electrode group, a pH electrode group, and a reference electrode channel. The array, containing a PtAu/CNT nanozyme modified with diboronic acid molecules, represents a pretreatment-free approach to evaluate glucose levels in human urine samples, exhibiting significantly enhanced selectivity for glucose. This study describes a novel technique for analyzing intricate samples and promoting home health monitoring. A comprehensive overview of certain other such sensors is depicted in Table 4.
Conclusion: summary, prospects, and challenges
In recent years, CNTs have been widely used for glucose detection because of their huge specific surface area, strong absorption capacity and superior electron transport capability. Here, we review the recent advances in CNT-based electrochemical sensors. Notably, this review highlights the current progress, challenges and future directions of electrochemical glucose sensors and briefly forecasts the future direct employment in body fluids.
Summary
In conclusion, this review has provided a comprehensive exploration of the design, manufacturing advancements, material synergies, and challenges associated with CNT-based electrochemical glucose sensors. Rapid progress in nanotechnology, microfluidics, miniaturization, and point-of-care sensing technology has spurred the development of sensitive, cost-effective, and user-friendly glucose monitoring tools. Researchers are actively integrating material design innovations, such as implantable and wearable microelectrodes and interstitial microneedles, to create a diverse array of adaptable CNT-based devices for biomarker detection in human biofluids. This review highlights the role of CNTs in high-performance wearable biosensors due to their flexibility and sub-nanometer thickness (equivalent to skin curvature) and predicts future advances in the detection of low glucose concentrations in a variety of body fluids and the integration of sensors into portable and implantable devices.
Challenges and improvements in CNT-based glucose sensors
The development and utilization of CNT-based glucose sensors come with several challenges and opportunities for improvement in various aspects of design, performance, and safety.
Heterogeneity of SWCNTs
One of the primary challenges is the heterogeneity of SWCNTs. The availability of pure, semiconducting SWCNTs is essential for electronic device applications. Techniques such as density gradient ultracentrifugation, dielectric electrophoresis, and surfactant dispersion are used for SWCNT dispersion. However, these methods often involve complex and tedious separation processes, impeding their widespread use [9].
Catalytic synergy
CNTs cannot directly catalyze glucose reactions. Hence, they require combination with other catalytic materials to enhance performance. Initially, enzymatic CNT-based sensors faced limitations due to sensitivity to ambient temperature and pH, restricting their broad applications. Researchers have substituted enzymes with metals, metal oxide compounds, alloys, MOFs, and conducting polymers (CPs) to enhance catalytic efficiency and practicality under various conditions. Effective synergy between CNTs and metals is crucial for optimal sensor performance.
Selectivity and stability of nonenzymatic sensors
While metal-based nonenzymatic sensors offer better stability and broader environmental suitability, they are susceptible to interference from oxidation intermediates and high chloride ion concentrations. Transition metal-based sensors are typically designed for alkaline environments, which contrast with the neutral environment of blood. Noble metals such as gold can function in diverse pH conditions but are expensive. Enhanced selectivity of nonenzymatic sensors integrated with metals and CNTs is essential, and molecular- or atomic-scale interactions should be explored for improved glucose monitoring properties.
Performance of CP nanomaterials
CP nanomaterials are commonly used in wearable glucose sensors due to their flexibility. However, issues such as poor selectivity, adsorption of intermediates, surface poisoning, and low sensitivity limit their application. The incorporation of CNTs with other nanomaterials can synergistically enhance the overall performance of CP-based sensors.
Improvement of flexibility and biocompatibility
The future direction of implantable biosensors is toward flexible and microfiber structures. CNT fibers are suitable for implantation due to their stable binding and compatibility with tissue [183, 184]. However, the inherent softness of CNT fibers can limit direct implantation [185]. Modification of fiber probes with polymer hydrogels with variable elastic modulus can enhance biocompatibility and minimize tissue damage during implantation.
Wearable sensor applications
In wearable sensor applications, CNTs are preferred for their excellent conductivity and flexibility. Fabric sensors offer advantages in terms of comfort, breathability, and durability compared to thin-film sensors. The development of multiplexed assays for diabetes-related markers using CNTs as platforms shows promise for comprehensive biosensing applications [186]. Flexible CNT fiber-based platforms can be integrated into textiles for real-time health monitoring, providing consistent and robust sensing capabilities [187].
The toxicity of CNTs
Future research should focus not only on the detection range but also on biocompatibility, stability, durability, and real-sample analysis to ensure practical usability. The controversy over the toxicity of CNTs requires careful consideration, especially in direct contact scenarios such as skin and lung exposure [188, 189].
Applications of CNT-based electrochemical glucose sensors for potential biological fluids
Owing to the demand for more convenient, diverse, and regionalized methods of detecting blood glucose, along with a need for rapid glucose response detection, the development and discussion of CNT-based electrochemical glucose sensors for multiple applications in various body fluids—including tears, exhaled breath condensate (EBC), nasal fluids, cerebrospinal fluid (CSF), and peritoneal fluid—are both necessary and meritorious.
While studies have brought to fruition CNT-based electrochemical glucose sensors for the detection of tear samples, the in-situ detection of tear glucose leveraging CNTs remains an unexplored territory. Properly prepared CNT films can attain a fusion of flexibility, light transmission, and electrical conductivity, aligning with the developmental trajectory of tear sensors [190]. Nonetheless, to date, tear sensors employing CNT films as substrates have not been found, a gap we perceive as a promising area of application.
EBC serves as a safe, noninvasive means for sampling fluids from the lower respiratory tract [191]. Since a primary challenge for EBC glucose sensors lies in the submicromolar sensitivity required [192, 193], sensors that integrate highly conductive CNTs into the EBC glucose sensing apparatus are ideally positioned to rectify such problems. Additionally, enzymatic sensors relying on H2O2 for indirect glucose content detection exhibit instability in EBC detection. If CNTs are employed to augment the performance of enzymatic glucose sensors, emphasis must be placed on enhancing enzyme stability. Similarly, respiratory fluids such as nasal fluid—which has not yet been definitively linked with blood glucose levels—are a novel and intriguing prospect in noninvasive glucose detection, even though electrochemical detection in nasal fluid remains undeveloped.
Furthermore, minimally invasive CNT-based glucose sensors for CSF and peritoneal fluids currently represent an uncharted area, and yet, they hold potential for future applications. Although detection in CSF is feasible under traumatic conditions, the pursuit of minimally invasive methods is still a promising avenue. To this point, implantable fiber biosensors based on CNTs have been designed to detect dopamine by probing deep brain tissue, but attempts to utilize electrochemical glucose sensors for CSF detection have yet to be made. Nonetheless, optimism prevails in the glucose detection domain. Importantly, no definitive evidence has been discovered regarding the toxicity of neural-related electrodes and biosensors founded on CNTs, and some reports even suggest that certain CNTs may promote cell growth [194, 195]. These findings may signify that CNTs are exceptionally promising materials for neural electrodes. Additionally, given the latency issues in subcutaneous continuous glucose monitoring (CGM), there have been proposals to utilize the intraperitoneal (IP) space for CGM [196]. Although the application of electrochemical glucose detection for IP is still in its infancy, the future likely holds promise for CNT-based electrochemical glucose sensors in IP applications, especially since CNTs can serve as flexible materials apt for long-term in vivo implantable detection.
It is vital to underscore that whether CNTs are employed as a fiber implantation material or as a dopant, careful consideration must be given to the in vivo safety of CNTs. This aspect should not be overlooked, even as strides are made to enhance sensor performance.
The promising applications of CNT-based glucose sensors in the field of biomedical sensing
Nanotechnology has emerged as a focal point in diverse biomedical applications, including cancer therapy, owing to its capacity to manipulate materials within the size range of 1–1000 nm [197, 198]. CNTs are perceived as suitable candidates for cancer therapy due to their unique structural, mechanical, electrical, and thermal properties (often referred to as PTT) [199]. The extensive surface area of CNTs facilitates the loading of high concentrations of anticancer therapeutics, either through the utilization of disulfides as linkers or via adsorption. Furthermore, controlled drug delivery can be orchestrated by modifying CNTs with stimuli-responsive materials [200].
Subsequently, a design paradigm has been postulated for a nanorobot capable of navigation, cancer cell detection in the bloodstream, and precise drug delivery [201]. By exploiting glucose hunger-based cancer detectors immobilized on CNT sensors, a decrease in electrical resistance occurs upon binding to cancer cells. This phenomenon triggers an electric current that activates a nanoelectromechanical relay, or a mechanical transistor, breaching the containment chamber and thereby exposing an immune system-recognized drug to obliterate the cell. This concept heralds a transformative approach for CNT-based glucose sensors, extending beyond macroscopic glucose monitoring in humans to include the assessment of glucose levels in the microscopic environments of cancer cells. The integration of bionanosensing with sophisticated nanotransistor technology marks a promising frontier for in vivo medical diagnostics and therapy.
Furthermore, investigations have been conducted into the skin permeability of CNTs for the transdermal administration of therapeutic agents. However, findings reveal that CNTs alone are not permeable through the skin, giving rise to a dilemma: noninvasive wearable CNT-based electrochemical glucose sensors are unable to concurrently function as drug application surfaces. Nevertheless, limited studies have demonstrated that lipid/polymer functionalization and ionic introduction can enhance the skin permeability of CNTs [202].
The collective evidence elucidated above galvanizes biomedical researchers to probe the capabilities of CNT-based glucose sensors in therapeutic contexts, a pursuit imbued with tremendous potential for unlocking novel milestones in biomedical sensing. In the foreseeable future, the reach of CNT-based electrochemical glucose sensors will likely transcend mere diagnostic sensing, with the incorporation of feedback mechanisms heralding a new era for therapeutic applications within diagnostic-therapeutic integrated devices.
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Acknowledgements
Guangchao Zang and Yuchan Zhang are grateful to Institute of Life Science, and Laboratory of Tissue and Cell Biology, Lab Teaching & Management Center, Chongqing Medical University, China for support. Guixue Wang and **angxiu Wang are grateful for the support provided by Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, China. Hanyan Zou would like to thanks the First Batch of Key Disciplines on Public Health in Chongqing and the Public Experiment Center of State Bioindustrial Base (Chongqing), China, and Finances from Chongqing Science and Technology Commission (CQIFDC-YJKT-2022-04)
Funding
This work was supported by grants the Science and Technology Innovation Project of **Feng Laboratory, Chongqing, China (jfkyjf202203001); the Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0330, cstc2021jsyjyzysbA0057); the National Natural Science Foundation of China (31971242, 12032007); the Project of Tutorial System of Medical Undergraduate in Lab Teaching & Management Center in Chongqing Medical University (LTMCMTS201913, LTMCMTS202111), the Project of Scientific Research and Innovative Experiment for College Student in Chongqing Medical University (SPIEP202167), and the National Project of University Students Innovation and Entrepreneurship Training Program (S202010631016). The First Batch of Key Disciplines on Public Health in Chongqing and the Public Experiment Center of State Bioindustrial Base (Chongqing), China, and Finances from Chongqing Science and Technology Commission (CQIFDC-YJKT-2022-04)
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TY: Conceptualization, investigation, methodology, project administration, validation, visualization, writing—original draft, writing—review & editing. DS: conceptualization, investigation, methodology, validation, writing—original draft, writing—review & editing. HZ: Funding acquisition, supervision, writing—review & editing. XY: Investigation, methodology, validation, writing—original draft, writing—review & editing. SW: Visualization, methodology, writing—review & editing. SZ: Investigation, writing—original draft, writing—review & editing. QL: Investigation. XW: Supervision, investigation. GW: Conceptualization, funding acquisition, supervision, validation, writing—original draft, writing—review & editing. YZ: Conceptualization, funding acquisition, project administration, supervision, validation, writing—original draft, writing—review & editing. GZ: Conceptualization, funding acquisition, methodology, project administration, supervision, validation, visualization, writing—original draft, writing—review & editing.
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Yuwen, T., Shu, D., Zou, H. et al. Carbon nanotubes: a powerful bridge for conductivity and flexibility in electrochemical glucose sensors. J Nanobiotechnol 21, 320 (2023). https://doi.org/10.1186/s12951-023-02088-7
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DOI: https://doi.org/10.1186/s12951-023-02088-7